Lecture 18 - Traffic Across Epithelial Cells: Chloride Secretion

What is the primary function of chloride secretion in epithelial tissues?

To hydrate mucosal surfaces and maintain fluid homeostasis by secreting chloride ions into the lumen, drawing water osmotically.

Where does chloride secretion mainly occur in the body?

In epithelial tissues such as the intestines, lungs, pancreas, and salivary glands.

What are the key steps in chloride secretion across epithelial cells?

1. Na⁺/K⁺-ATPase maintains low intracellular Na⁺. 2. NKCC1 transports Cl⁻, Na⁺, and K⁺ into the cell from the basolateral side. 3. K⁺ leaks out via channels. 4. Cl⁻ exits apically via CFTR. 5. Na⁺ and water follow paracellularly.

What is the role of NKCC1 in chloride secretion?

NKCC1 is a secondary active transporter on the basolateral membrane that brings Na⁺, K⁺, and Cl⁻ into the cell, driven by the Na⁺ gradient.

What is the CFTR channel?

Cystic Fibrosis Transmembrane Conductance Regulator: a cAMP-regulated Cl⁻ channel on the apical membrane of epithelial cells.

How is CFTR activated?

Via phosphorylation by Protein Kinase A (PKA) in response to cAMP signalling.

What causes secretory diarrhoea?

Bacterial enterotoxins (e.g., cholera toxin) increase cAMP, overstimulating CFTR, causing excessive Cl⁻ and water secretion.

What is the clinical result of overstimulated CFTR in secretory diarrhoea?

Massive fluid loss into the intestinal lumen → dehydration and electrolyte imbalance.

What is Cystic Fibrosis (CF)?

A genetic disorder caused by mutations in the CFTR gene, leading to defective or absent Cl⁻ secretion.

What are the effects of defective CFTR in Cystic Fibrosis?

Thick, sticky mucus in lungs and pancreas due to lack of Cl⁻ and water secretion → respiratory infections and pancreatic insufficiency.

Why is the mucus thick in CF patients?

Because Cl⁻ cannot be secreted properly, water does not follow, leading to dehydrated mucus.

How does CF affect sweat glands differently?

CFTR is in sweat glands; without it, Cl⁻ is not reabsorbed → sweat is abnormally salty.

How does CF affect the lungs?

Mucociliary clearance is impaired, leading to chronic lung infections due to mucus buildup.

How does CF affect the pancreas?

Thickened secretions block pancreatic ducts, preventing enzyme release → malabsorption and nutrient deficiencies.

What is the most common mutation in CFTR?

ΔF508: deletion of phenylalanine at position 508, causing CFTR misfolding and degradation before reaching the membrane.